Three-dimensional Printing System and Equipment Assembly

ABSTRACT

A three-dimensional printing system and equipment assembly for the manufacture of three-dimensionally printed articles is provided. The equipment assembly includes a three-dimensional printing build system, an optional liquid removal system and an optional harvester system. The build system includes a conveyor, plural build modules and at least one build station having a powder-layering system and a printing system. The equipment assembly can be used to manufacture pharmaceutical, medical, and non-pharmaceutical/non-medical objects. It can be used to prepare single or multiple articles.

CROSS-REFERENCE TO EARLIER FILED APPLICATIONS

This application is a continuation of and claims the benefit of U.S.Ser. No. 15/046,714 filed Feb. 18, 2016, which is a continuation of U.S.Ser. No. 14/501,716 filed Sep. 30, 2014, which is a continuation of U.S.Ser. No. 14/016,697, filed Sep. 3, 2013, now U.S. Pat. No. 8,888,480,issued Nov. 18, 2014, which is a continuation of and claims the benefitof PCT/US2013/057466 filed Aug. 30, 2013, which claims the benefit ofprovisional application 61/696,839 filed Sep. 5, 2012, the entiredisclosures of which are hereby incorporated by reference.

FIELD OF THE INVENTION

The present invention concerns a manufacturing system and equipmentassembly and use thereof for the preparation three-dimensional printingof articles from one or more powders and one or more liquids applied tothe powder.

BACKGROUND OF THE INVENTION

Rapid prototyping describes various techniques for fabricating athree-dimensional prototype of an object from a computer model of theobject. One technique is three-dimensional printing, whereby a printeris used to fabricate the 3-D prototype from a plurality oftwo-dimensional layers. In particular, a digital representation of a 3-Dobject is stored in a computer memory. Computer software sections therepresentation of the object into a plurality of distinct 2-D layers.Alternatively, a stream (sequential series) of instructions for eachincremental layer maybe entered directly, e.g. a series of images. A 3-Dprinter then fabricates a thin layer of bound material for each 2-Dimage layer sectioned by the software. Together, the layers are printedone on top of the other and adhere to each other to form the desiredprototype.

Three-dimensional powder-liquid printing technology has been used toprepare articles such as pharmaceutical dosage forms, mechanicalprototypes and concept models, molds for casting mechanical parts, bonegrowth promoting implants, electronic circuit boards, scaffolds fortissue engineering, responsive biomedical composites, tissue growthpromoting implants, dental restorations, jewelry, fluid filters andother such articles.

Three-dimensional printing is a solid freeform fabricationtechnique/rapid-prototyping technique in which thin layers of powder arespread onto a surface and selected regions of the powder are boundtogether by the controlled deposition (“printing”) of a fluid. Thisbasic operation is repeated layer-by-layer, with each new layer formedon top of and adhered to the previously printed layer, to eventuallymake three-dimensional objects within a bed of unbound powder. When theprinted objects have sufficient cohesion, they may be separated from theunbound powder.

Systems and equipment assemblies for three-dimensional printing ofarticles are commercially available or in use by others: MassachusettsInstitute of Technology Three-Dimensional Printing Laboratory(Cambridge, Mass.), Z Corporation's 3DP and HD3DP™ systems (Burlington,Mass.), The Ex One Company, L.L.C. (Irwin, Pa.), Soligen (Northridge,Calif.), Specific Surface Corporation (Franklin, Mass.), TDK Corporation(Chiba-ken, Japan), Therics L.L.C. (Akron, Ohio, now a part of IntegraLifesciences), Phoenix Analysis & Design Technologies (Tempe, Ariz.),Stratasys, Inc.'s Dimension™ system (Eden Prairie, Minn.), ObjetGeometries (Billerica, Mass. or Rehovot, Israel), Xpress3D (Minneapolis,Minn.), and 3D Systems' Invision™ system (Valencia, Calif.).

Some systems have been described in the patent literature: U.S.Publications No. 20080281019, No. 20080277823, No. 20080275181, No.20080269940, No. 20080269939, No. 20080259434, No. 20080241404, No.20080231645, No. 20080229961, No. 20080211132, No. 20080192074, No.20080187711, No. 20080180509, No. 20080138515, No. 20080124464, No.20080121172, No. 20080121130, No. 20080118655, No. 20080110395, No.20080105144, No. 20080068416, No. 20080062214, No. 20080042321, No.20070289705, No. 20070259010, No. 20070252871, No. 20070195150, No.20070188549, No. 20070187508, No. 20070182799, No. 20070182782, No.20070168815, No. 20070146734, No. 20060268057, No. 20060268044, No.20060230970, No. 20060141145, No. 20060127153, No. 20060111807, No.20060110443, No. 20060099287, No. 20060077241, No. 20050054039, No.20060035034, No. 20060030964, No. 20050247216, No. 20050204939, No.20050197431, No. 20050179721, No. 20050104241, No. 20050069784, No.20050061241, No. 20050059757, No. 20040265413, No. 20040262797, No.20040252174, No. 20040243133, No. 20040225398, No. 20040187714, No.20040183796, No. 20040145781, No. 20040145628, No. 20040145267, No.20040143359, No. 20040141043, No. 20040141030, No. 20040141025, No.20040141024, No. 20040118309, No. 20040112523, No. 20040056378, No.20040012112, No. 20040005360, No. 20040005182, No. 20040004653, No.20040004303, No. 20040003741, No. 20040003738, No. 20030207959, No.20030198677, No. 20030143268, No. 20020125592, No. 20020114652, No.20020079601, No. 20020064745, No. 20020033548, No. 20020015728, No.20010028471, and No. 20010017085; U.S. Pat. Nos. 5,490,962, 5,204,055,5,121,329, 5,127,037, 5,252,264, 5,340,656, 5,387,380, 5,490,882,5,518,680, 5,717,599, 5,851,465, 5,869,170, 5,874,279, 5,879,489,5,902,441, 5,934,343, 5,940,674, 6,007,318, 6,146,567, 6,165,406,6,193,923, 6,200,508, 6,213,168, 6,336,480, 6,363,606, 6,375,874,6,416,850, 6,508,971, 6,530,958, 6,547,994, 6,596,224, 6,772,026,6,838,035, 6,850,334, 6,905,645, 6,945,638, 6,989,115, 7,220,380,7,291,002 7,365,129, 7,435,368, 7,455,804, 7,686,955, 7,828,022,8,017,055; PCT International Publications No. WO 00/26026, No. WO98/043762, No. WO 95/034468, No. WO 95/011007; and European Patent No.1,631,440, which employs a cylindrical (radial or polar)coordinate-based system due to its construction.

Three-dimensional printing systems that employ radial or polarcoordinate-based printing systems are disadvantageous because havingeach jetting position located at a different radial position requiresthat the surface speed of the substrate underneath the each jettingposition will vary. The surface speed will be greatest for the jettingposition furthest from the center of rotation. This can be compensatedfor by normalizing the print density across all jetting positions byeither adjusting the input images or possibly the drive frequency.However, these methods of compensation simply cause objects printedradially to emulate each other as opposed to true replicates. The angleof entry of the droplets into the powder bed will also vary with radialposition again creating subtle differences in the objects printed atdifferent locations. Alignment and interleaving of multiple print headsis another disadvantage to radially printing. Although feasible it ismore complex than for Cartesian systems.

SUMMARY OF THE INVENTION

The present invention provides a manufacturing system and equipmentassembly useful for the preparation of articles by three-dimensionalprinting. The system and assembly can be used for high through-putcontinuous, semi-continuous, or batch manufacture with minimal productloss, high efficiency, and high product reproducibility in the contextof flexible article design.

The invention provides a three-dimensional printing equipment assemblycomprising:

-   -   a) a three-dimensional printing build system comprising:    -   a conveyor system adapted to conduct plural build modules;    -   plural build modules engaged with the conveyor system, wherein        the build modules are adapted to receive and temporarily retain        powder from a powder layering system; and    -   at least one build station comprising: 1) at least one powder        layering system adapted to form incremental powder layers within        build modules; and 2) at least one printing system adapted to        apply a liquid according to a predetermined pattern to        incremental powder layers within build modules;    -   wherein the conveyor system repeatedly transports the build        modules from the at least one powder layering system to the at        least one printing system to form a three-dimensionally printed        bed comprising one or more three-dimensionally printed articles        in the build modules.

In some embodiments, the three-dimensional printing equipment assemblyfurther comprises at least one liquid removal system adapted to receiveone or more three-dimensionally printed beds and to remove liquid fromone or more powder layers onto which the liquid has been applied and/orfrom the three-dimensionally printed bed.

In some embodiments, a build module comprises an incrementally heightadjustable platform adapted to receive and temporarily retain at leastone incremental layer or plural stacked incremental layers of powder. Insome embodiments, a build module comprises a body comprising an uppersurface with a cavity, a height adjustable build platform disposedwithin the cavity, height adjuster engaged with the body and theplatform, and engagement means. In some embodiments, plural buildmodules are removably engaged with the conveyor system. In someembodiments, the platform is adapted to lower (recess) and/or raise byone or more increments after placement of an incremental layer of powderthereon. The platform displacement can occur prior to or after placementof a subsequent incremental layer of powder thereon, therebypress-rolling or removing a portion of powder from a powder layer thathas already been laid down. In some embodiments, the size of anincrement is predetermined. In some embodiments, the build modulecomprises one or more sidewalls surrounding the build plate and beingadapted to retain powder on the height adjustable platform. In someembodiments, the build module further comprises a removable build platedisposed below the upper surface of the build module. In someembodiments, the removable build plate is disposed above the heightadjustable platform and is adapted to receive and support one or moreincremental layers of powder. In some embodiments, the removable buildplate is flat, porous, perforated, textured, coated, knurled, smooth ora combination thereof. In some embodiments, engagement means are adaptedto removably engage a build module with the conveyor system.

In some embodiments, the conveyor system conducts the plural buildmodules along a planar circuitous path, a horizontal circuitous path, avertical circuitous path, or a combination thereof. In some embodiments,the conveyor system is adapted to transport plural build modules along apath in a counterclockwise direction or clockwise direction. In someembodiments, the path of the modular conveyor system is circular,ellipsoidal, rectangular, semicircular, square, triangular, pentagonal,hexagonal, octagon, oval, polygonal, parallelogram, quadrilateral,geometric, symmetrical, asymmetrical, or equivalents thereof withrounded corners and/or edges. In some embodiments, the modular conveyorsystem comprises plural conveyor modules, at least one drive motor, atleast one positioning controller, and a path along which plural buildmodules are conducted. In some embodiments, a conveyor module comprisesa body, one or more build module engagement means, and conveyor moduleengagement means by way of which plural conveyor modules are adapted toengage to form a modular conveyor. In some embodiments, the conveyorsystem comprises plural attachments adapted to removably retain theplural build modules. In some embodiments, the attachment comprisesplural one or more metal links with cam followers or comprises wheels,plates and/or bearings attached to a build module and mounted on a railsystem upon which the build module is conducted. In some embodiments,the conveyor system further comprises one or morepositioning-controllers. In some embodiments, the conveyor system is acontinuous or discontinuous loop system.

In some embodiments, the at least one build station is incrementallyheight adjustable with respect to the build modules, whereby thevertical space between the build module and the build station can beadjusted by one or more increments. In some embodiments, anincrementally height adjustable build station is adapted to raise by oneor more increments after placement of a layer of powder on a buildmodule and prior to placement of a subsequent layer of powder the buildmodule. In some embodiments, a change in height is achieved by changingvertical position with respect to a prior position of the platform orwith respect to an absolute position of the platform relative to thebuild module. In some embodiments, the build station is vertically fixedwith respect to the build modules and a build platform within a buildmodule is vertically height adjustable with respect to the build moduleso that the vertical distance between the build station and the buildmodule remains the same during a print lap or print cycle.

In some embodiments, the size of the increment is the same for eachincremental layer of a build cycle, is different for one or moreincremental layers of a build cycle or a combination thereof. A buildcycle comprises one or more build laps or plural build laps and isdefined as the sum total of build laps required to form a 3DP article. Abuild lap is defined as the process of forming a printed incrementallayer, i.e. placing an incremental layer of powdered build material anddepositing (printing) liquid upon it. Accordingly, a build cycle resultsin the formation of plural stacked printed incremental layers thatadhere to one another to together form a three-dimensionally printedarticle.

In some embodiments, the at least one powder layering system comprisesat least one powder fill head. In some the embodiments, the powder fillhead is stationary, meaning it does not move, either longitudinally ortransversely with respect to the plane of the upper surface of a buildmodule, when applying an incremental layer of powder onto the buildmodule. In some embodiments, a powder fill head comprises at least onepowder fill head body, at least one powder spreader, and at least onepowder-height controller. In some embodiments, a powder layering systemcomprises a powder fill head, at least one powder reservoir and a powderfeeder tube adapted to transfer powder from the powder reservoir to thepowder fill head. In some embodiments, the powder spreader is acylindrical roller the axis of which has or defines a radial directionof motion opposite the linear direction of motion of a build modulethrough the powder layering system. In some embodiments, the powderspreader is a cylindrical roller, bar, rod, plate or straight smoothedge. In some embodiments, the powder fill head comprises a hopper orchute.

In some embodiments, the at least one printing system is adapted toapply (deposit) liquid to the powder according to a Cartesian coordinatealgorithm instead of a polar (radial) coordinate algorithm (cylindricalcoordinate system, circular coordinate system, or spherical coordinatesystem). In some embodiments, the printing system comprises at least oneprint head adapted to deposit liquid onto an incremental layer of powderin a build station and at least one liquid feed system. A print head cancomprise one or more print modules or plural print modules. In someembodiments, the invention excludes a printing system adapted to applyliquid to the powder solely according to a polar (radial) coordinatesystem. In some embodiments, the invention excludes an equipmentassembly or a method wherein the powder fill head moves laterally ortransversely or is not stationary, with respect to a build module, whiledepositing an incremental powder layer. In some embodiments, theinvention excludes an equipment assembly or a method wherein the printhead moves laterally or transversely or is not stationary, with respectto a build module, while applying liquid to an incremental powder layer.

In some embodiments, the at least one printing system is adapted toapply (deposit) liquid as a three-dimensional pattern of droplets or asplural two-dimensional patterns of droplets defining one or morearticles. In some embodiments, the pattern comprises droplets placed atequal spacing within one or more articles. In some embodiments, thispattern comprises droplets placed at unequal spacing within one or morearticles. In some embodiments, this pattern comprises droplets withdifferent spacing within different regions of an article. In someembodiments, this pattern comprises droplets with tighter spacing (i.e.,higher print density) in a region defining the exterior of an article.In some embodiments, this pattern comprises droplets with looser spacing(i.e., lower print density) in a region interior to an article.

In some embodiments, more than one pattern is used. In some embodiments,more than one liquid is used. In some embodiments, the liquid comprisesa pure solvent, blend of solvents, solution, suspension, colloid,emulsion, melt or a combination thereof.

In some embodiments, both the print head and the powder fill head arestationary during formation of a printed incremental layer or arestationary as otherwise described herein.

In some embodiments, the equipment assembly further comprises a bedtransfer system adapted to transfer three-dimensionally printed beds,one or more at a time, away from the three-dimensional printing buildsystem. In some embodiments, the bed transfer system is adapted totransfer three-dimensionally printed beds to one or more liquid removalsystems and/or one or more harvesting systems. In some embodiments, thetransfer system is integrated with the conveyor system, the liquidremoval system or both.

In some embodiments, the liquid removal system comprises at least onedryer. In some embodiments, the liquid removal system is adapted toprocess two or more build plates and their contents at a time. In someembodiments, the liquid removal system is adapted to process two or moreprinted beds at a time. In some embodiments, the liquid removal systemis adapted to process two or more printed articles at a time.

In some embodiments, the three-dimensionally printed powder bedcomprises loose (unbound) powder and one or more three-dimensionallyprinted articles prior to harvesting of the printed article(s) from theloose powder. In some embodiments, the equipment assembly comprises oneor more harvesting systems adapted to separate loose powder from the oneor more three-dimensionally printed articles. In some embodiments, theharvesting system processes printed beds already processed by the liquidremoval system. In some embodiments, the harvesting system comprisesloose powder collector and three-dimensionally printed articlecollector. In some embodiments, the harvesting system comprises avibrating or orbiting surface adapted to receive the three-dimensionallyprinted powder bed or the three-dimensionally printed articles. In someembodiments, the harvesting system comprises a vacuum conveyor with ascreen to separate articles from loose powder. The vibrating surface canbe perforated, non-perforated, corrugated, smooth or non-smooth topermit separation of loose powder from the printed articles.

In some embodiments, the equipment assembly further comprises adedusting system adapted to remove loose particles from printed articlesthat have been harvested from a printed powder bed. A dedusting systemcan comprise a housing defining a dedusting region, one or more airjets, e.g. one or more air knives, that direct pressurized air into thededusting region, one or more surfaces or retainers in the dedustingregion for temporarily retaining one or more printed articles beingdedusted, and one or more outlets through which air and removedparticles exit the housing or dedusting region.

In some embodiments, the equipment assembly further comprises a buildplate loading system adapted to place one or more build plates on theheight adjustable platform(s) of the one or more build modules.

In some embodiments, the equipment assembly further comprises one ormore powder recovery systems adapted to collect powder from the one ormore systems of the equipment assembly and return it to a powderreservoir. The recovery system can comprise one or more loose powdercollectors and one or more conduits for conducting loose powder from theone or more collectors to a powder reservoir. The recovery system canfurther comprise: a) one or more powder mixers for mixing recoveredloose powder with virgin loose powder; b) one or more pressurized airpowder handling systems that facilitate transfer of loose powder fromone location to another; c) one or more vacuum powder handling systemsthat facilitate transfer of loose powder from one location to another;d) one or more mechanical powder handling systems that transfer loosepowder from one location to another; e) one or more manual powderhandling systems that transfer loose powder from one location toanother; or a combination thereof.

In some embodiments, the equipment assembly further comprises a controlsystem comprising one or more computerized controllers, one or morecomputers, and one or more user interfaces for one or more computers. Insome embodiments, one or more components of the equipment assembly arecomputer controlled. In some embodiments, one or more components of thethree-dimensional printing build system are computer controlled. In someembodiments, the conveyor system, the height adjustable platforms of thebuild modules, the at least one powder layering system and the at leastone printing system are computer controlled. In some embodiments, theequipment assembly is adapted to spread layers of powder and deposit(print) droplets of liquid in a predetermined pattern on to the layersaccording to instructions provided by a computerized controller. In someembodiments, the predetermined pattern is based on one or moretwo-dimensional image files comprising pixels. In some embodiments, thetwo-dimensional image files are structured such that certain pixelsindicate dispensing of droplets, and other pixels represent nodispensing of droplets. In some embodiments, the two-dimensional imagefiles include different colors of pixels to indicate dispensing ofdifferent liquids, or no dispensing of liquid.

In some embodiments, the predetermined pattern for applying the liquidis the same in each incremental layer, is the same in two or moreincremental layers, is different in one or more incremental layers, isdifferent in all incremental layers, or is the same for a first group ofincremental layer and the same for a second group of incremental layersbut the pattern for the first group is different than the pattern forthe second group.

In some embodiments, the equipment assembly further comprises one ormore working surfaces, tables, gantries, enclosures, and/or platforms.

The invention also provides a three-dimensional printing equipmentassembly comprising:

-   -   a) a three-dimensional printing build system comprising:    -   a conveyor system adapted to conduct plural build modules and        comprising positioning-controller and plural build module        engagements;    -   plural build modules engaged with the conveyor system, wherein        the build modules are adapted to receive and temporarily retain        powder from a powder layering system, and wherein a build module        comprises an incrementally height adjustable platform, an        optional build plate disposed above the platform, and one or        more sidewalls defining a cavity within which the platform the        optional build plate can be disposed;    -   at least one build station comprising: 1) at least one powder        layering system adapted to form incremental powder layers within        the cavity of build modules and comprising at least one powder        fill head, at least one powder spreader and at least one powder        reservoir; and 2) at least one printing system adapted to apply        a liquid according to a predetermined pattern to incremental        powder layers within build modules and comprising at least one        liquid feed system and at least one print head adapted to        deposit liquid according to a predetermined pattern onto        incremental layers of powder in a build module;    -   wherein the conveyor system is adapted to repeatedly transport        the plural build modules from the at least one powder layering        system to the at least one printing system,    -   whereby the three-dimensional printing build system forms a        three-dimensionally printed bed comprising one or more        three-dimensionally printed articles, and optionally loose        (unbound or only partially bound) powder that has not been        printed upon;    -   b) at least one harvesting system adapted to separate loose        powder from one or more three-dimensionally printed articles in        a three-dimensionally printed bed; and    -   c) optionally, at least one liquid removal system adapted to        remove liquid from one or more incremental powder layers onto        which the liquid has been applied and/or from the        three-dimensionally printed bed, wherein the liquid removal        system is adapted to process two or more build modules at a        time.

Some embodiments of the invention include those wherein: 1) at least oneliquid removal system is present; 2) the equipment assembly furthercomprises at least one packaging system adapted to package one or morethree-dimensionally printed articles; 3) the conveyor system is adaptedto repeatedly transport the plural build modules, from the at least onepowder layering system to the at least one printing system, in a linearmanner, and not a radial manner, thereby facilitating Cartesiancoordinate printing and not radial (polar coordinate) printing; 4) theequipment assembly further comprises a powder recovery system forrecovering, and optionally recycling, unprinted powder; 5) the equipmentassembly further comprises a liquid detector; 6) a liquid detectordetects the presence of liquid in one or more printed incremental layersand/or in one or more printed articles; 7) the equipment assemblyfurther comprises an inspection system; 8) an inspection system is aprinted powder inspection system that determines the integrity ofprinting in one or more printed incremental layers and/or one or moreprinted articles and/or determines whether or not powder was properlyapplied in one or more incremental layers; 9) determining the integrityof printing comprises at least one of determining whether or not liquidhas been correctly applied to one or more incremental layers accordingto one or more predetermined patterns and/or determining whether or notliquid has been correctly applied to one or more incremental layersaccording to a predetermined amount; 10) the inspection system is aprinted article inspection system that determines whether or not one ormore printed articles have the correct size, shape, weight, appearance,density, content and/or color; 11) the inspection system is a liquidapplication inspection system that monitors droplets of liquid appliedby the print head to powder; 12) the inspection system comprises one ormore cameras; and/or 13) a camera is independently selected at eachoccurrence from the group consisting of a visible wavelength camera, anUV wavelength camera, a near infrared wavelength camera, an x-ray cameraand an infrared wavelength camera.

The invention includes all combinations of the embodiments,subembodiments and aspects disclosed herein. Accordingly, the inventionincludes the embodiments and aspects specifically disclosed, broadlydisclosed, or narrowly disclosed herein, as well as combinations thereofand subcombinations of the individual elements of said embodiments andaspects.

Other features, advantages and embodiments of the invention will becomeapparent to those skilled in the art by the following description,accompanying examples.

BRIEF DESCRIPTION OF THE FIGURES

The following figures form part of the present description and describeexemplary embodiments of the claimed invention. These drawings are notnecessarily drawn to scale, and are instead intended to illustrate thegeneral principles of the invention as further described herein.Although specific embodiments are described below with specificreference to the drawings provided, other embodiments are possiblewithout deviating from the spirit and scope of the present invention.The skilled artisan will, in light of these figures and the descriptionherein, be able to practice the invention without undue experimentation.

FIG. 1 depicts a top plan view of an exemplary layout of athree-dimensional printing equipment assembly of the invention.

FIG. 2A depicts a front elevation view of an exemplary build module ofthe invention.

FIG. 2B depicts a partial perspective side view of the build module ofFIG. 2A.

FIG. 2C depicts a front elevation view of a three segments of asegmented or modular conveyor system.

FIG. 2D depicts a top plan view of the three segments of FIG. 2C.

FIG. 2E depicts a side elevation view of an optional exemplaryaspirator.

FIG. 3A depicts a top plan view of an exemplary printing system of theinvention.

FIG. 3B depicts a side elevation view of the exemplary printing systemof FIG. 3A.

FIG. 3C depicts a front elevation view of the exemplary printing systemof FIG. 3A.

FIG. 4 depicts a bottom perspective view of an exemplary layout of printmodules in the print head of a printing system.

FIG. 5 depicts bottom plan views of alternate exemplary layouts for theprint modules in different print heads.

FIG. 6 depicts alternate exemplary shapes of the build plates of theinvention.

FIG. 7A depicts a top plan view of an exemplary build plate loadingsystem of the invention.

FIG. 7B depicts a side elevation view of the exemplary build plateloading system of FIG. 7A.

FIG. 8A depicts a top plan view of an exemplary powder layering systemof the invention.

FIG. 8B depicts a side elevation view of the exemplary powder layeringsystem of FIG. 8A.

FIG. 8C depicts a front elevation view of the exemplary powder layeringsystem of FIG. 8A.

FIG. 9 depicts a perspective view of an exemplary powder fill head ofthe invention.

FIG. 10A depicts a top plan view of an exemplary bed transfer system ofthe invention.

FIG. 10B depicts a side elevation view of the exemplary bed transfersystem of FIG. 10A.

FIG. 10C depicts a partial top plan view of an alternated exemplary bedtransfer system.

FIGS. 11A-11B depict partial sectional side elevation views of alternateembodiments of exemplary three-dimensional printing processes in a buildmodule of the invention.

FIGS. 12A-12D depict top plan views of exemplary layouts of athree-dimensional printing build system of the invention.

FIG. 12E depicts a side elevation view of an exemplary layout of athree-dimensional printing build system of the invention.

FIG. 13A depicts a partial sectional side elevation view of an exemplarydryer or fluid removal system of the invention.

FIG. 13B depicts a partial sectional side elevation view of an alternateexemplary dryer or fluid removal system of the invention.

FIG. 14 depicts a side elevation view of an exemplary harvesting systemof the invention.

FIG. 15 depicts a side elevation view of an exemplary packaging systemof the invention.

FIG. 16 depicts a partial top plan view of an exemplary build stationcomprising a powder layering system and a print head.

FIGS. 17A-17D depict top plan views of various different embodiments ofa print head and arrangements thereof.

FIG. 18 depicts a perspective view of a combination harvester system anddeduster or dedusting system assembly.

FIGS. 19A-19C together depict an exemplary logic flow for operation ofthe equipment assembly of the invention. FIG. 19A continues to FIG. 19B,which continues to FIG. 19C, which refers back to FIG. 19A.

FIG. 20 depicts an exemplary logic flow for operation of the powderlayering system.

FIG. 21 depicts an exemplary logic flow for operation of the printingsystem.

FIG. 22 depicts an exemplary logic flow for design of a dosage form.

DETAILED DESCRIPTION OF THE INVENTION

The invention provides an equipment assembly and system useful for themanufacture of articles via a three-dimensional printing process. Theassembly and system are suitable for small scale/volume, mediumscale/volume and large scale/volume preparation of articles. Thethree-dimensional printing process comprises forming an incrementallayer of powder on a surface and subsequently printing/applying a liquidonto the layer, then repeating the steps of forming and printing asufficient number of times to form a printed powder bed comprising oneor more intended three-dimensionally printed articles and loose powder.Any excess/undesired liquid remaining in the article(s) is removed andthe loose powder is separated from the article, which is then collected.

Generally, a three-dimensional printing equipment assembly or systemcomprises various subsystems including one or more three-dimensionalprinting build systems, one or more harvesting systems, and optionallyone or more liquid removal systems. The equipment assembly can compriseone or more three-dimensional printing build systems, one or moreharvesting systems, one or more liquid removal systems and optionallyone or more other systems. In some embodiments, the equipment assemblyfurther comprises one or more (sub)systems selected from one or morebuild plate loading systems, one or more powder recovery systems, one ormore control systems, one or more build module or conveyor positioningsystems, one or more conveyor drive motors, one or more bed transfersystems, or a combination of systems thereof.

As used herein, a “three-dimensional printing build system” generallycomprises a conveyor system, plural build modules, at least one buildstation, and optionally one or more other components. The function ofthe three-dimensional printing build system is to form one or morethree-dimensionally printed articles from a multilayered bed of powderin a build module. Plural build modules are engaged with a conveyorsystem that is adapted to conduct the build modules along apredetermined path which passes through one or more build stations. Abuild module is conducted to a powder layering system, and anincremental layer of powder is formed on the upper surface of a cavityof a build module. The build module is then conducted to a printingsystem, and a liquid is applied to the incremental layer of powderaccording to a predetermined pattern thereby forming a partially orfully bound powder layer (a printed incremental layer). The steps ofconducting the build module, forming an incremental layer of powder andapplying a liquid to the layer are considered to be a single build lapof the process. Build laps are repeated in build modules such that aprinted incremental layer from one lap adheres to a printed incrementallayer from a prior or subsequent lap. Build laps are repeated in buildmodules a sufficient number of times to form a three-dimensionallyprinted bed comprising one or more three-dimensionally printed articlesand loose powder, wherein the three-dimensionally printed articlecomprises at least two printed incremental layers. The liquid applied tothe pattern may or may not dry sufficiently under ambient conditionsbetween build laps; therefore, a liquid removal step can be includedbetween build laps. If, however, the liquid does not dry sufficientlybetween build laps, then an optional liquid removal step can beconducted following completion of all the build laps, i.e. followingcompletion of a build cycle, for an intended three-dimensionally printedarticle.

The conveyor system is adapted to conduct build modules through apredetermined course/path during and between build laps. Substantiallyany system useful for conveying solid materials from a first location toa second location and back to the first location can be used. In someembodiments, the conveyor system is a cyclic, linear or oscillatingconveyor system. In some embodiments, the cyclic conveyor systemconducts build modules from the first location to a second location andthen back to the first location. In some embodiments, the conveyorsystem is a cyclic or iterative conveyor system that conducts buildmodules two or more times through the same build station(s). In someembodiments, the linear conveyor system conducts build modules from afirst build station to a second build station and optionally one or moreother build stations. In some embodiments, the oscillating systemconducts one or more build modules through at least one build station ina first direction and then conducts the one or more build modulesthrough the at least one build station in an opposite direction.

FIG. 1 depicts a top plan view of an exemplary three-dimensionalprinting equipment assembly (1) comprising a conveyor (2) adapted toconduct plural build modules (6) engaged with the conveyor system alonga predetermined path through build regions in one or more buildstations, respectively, comprising: a) at least one powder layeringsystem (3) adapted to form incremental powder layers within buildmodules; and b) at least one printing system (4) adapted to apply aliquid according to a predetermined pattern to incremental powder layerswithin build modules. The build modules are adapted to receive andtemporarily retain powder from the powder layering system. In the cyclicsystem depicted, the conveyor system is a continuous loop system thatrepeatedly transports/cycles the build modules from the at least onepowder layering system to the at least one printing system to form athree-dimensionally printed bed comprising one or morethree-dimensionally printed articles in the build modules. The exemplaryconveyor system (2) comprises at least one drive (12) and pluralconveyor modules (2 a), thereby forming a segmented or modular conveyorsystem. A conveyor module is engaged with a corresponding build moduleand conducted along a predetermined pathway in the direction of Arrow A.

The equipment assembly in FIG. 1 is depicted finishing three-dimensionalprinting of a first batch of 3-D (three dimensional) articles andstarting the 3-D printing of a second batch of 3-D articles. Athree-dimensionally printed bed from the end of a first build cycle isin build module (6 a), and the beginning of the second batch starts witha printed incremental layer in build module (6L). Build module (6 a)includes six 3-D articles in a printed bed of powder. As the buildmodules (6, 6 a-6L) are conducted along the predetermined course, theypass through the bed transfer system (8), which transfers build platescontaining completed three-dimensionally printed beds, one or more at atime, away from the three-dimensional printing build system. A buildmodule comprises a body (7 a), and upper surface (7 c) having a cavitywith in which a height adjustable build platform (7 b) is disposed. Anempty build module (6 g) optionally receives a build plate (10) as itpasses through the build plate loading region of an optional build plateloading system (9). The build module (6 h) is now ready to receivepowder. Build modules will pass through at least one build stationcomprising at least one powder layering system (3) and at least oneprinting system (4).

The build module (6 j) is depicted passing through the powder dispensingregion of a powder layering system (3). The build module (6 k) isdepicted between the powder layering system (3) and the printing system(4) and in the recovery region of an optional powder recovery system(11), which pick ups loose powder from the upper surface of buildmodules. The build module (6L), which is the first build module of thenext build lap, is depicted passing through the printing region of theprinting system (4). A control system, comprising at least one or morecomputers and one or more use interfaces (5), can be used to control andintegrate (coordinate) operation of the various components and systemsof the equipment assembly (1). In some embodiments, operation of each ofthe conveyor system, the height adjustable platforms of the buildmodules, the at least one powder layering system, and the at least oneprinting system are controlled by the control system. In someembodiments, operation of one or more of the build plate loading system(9), optional powder recovery system (11) and bed transfer system iscontrolled by the control system.

An equipment assembly can further comprise a bed transfer system (8)adapted to transfer three-dimensionally printed beds, one or more at atime, away from the three-dimensional printing build system. Theexemplary bed transfer system (8) depicted is adapted to simultaneouslyremove two or more printed beds from respective build modules in a bedtransfer region. In some embodiments, the bed transfer system is adaptedto transfer three-dimensionally printed beds and corresponding buildplates (and/or build modules), one or more at a time, away from thethree-dimensional printing build system.

In some embodiments, a three-dimensional printing equipment assemblycomprises:

-   -   a) a three-dimensional printing build system comprising:    -   a conveyor system adapted to conduct plural build modules;    -   plural build modules engaged with the conveyor system, wherein        the build modules are adapted to receive and temporarily retain        powder from a powder layering system; and    -   at least one build station comprising: 1) at least one powder        layering system adapted to form incremental powder layers within        build modules temporarily disposed in a powder dispensing region        of the build station; and 2) at least one printing system        adapted to apply a liquid according to a predetermined pattern        to incremental powder layers temporarily disposed within build        modules in a printing region of the build station;    -   wherein the conveyor system repeatedly transports the build        modules from the powder dispensing region of the at least one        powder layering system to the printing region of the at least        one printing system to form a three-dimensionally printed bed        comprising one or more three-dimensionally printed articles in        the build modules;    -   b) at least one bed transfer system adapted to transfer        completed three-dimensionally printed beds, one or more at a        time, away from the build region of the three-dimensional        printing build system;    -   c) at least one harvesting system adapted to separate loose        powder from one or more three-dimensionally printed articles in        a three-dimensionally printed bed;    -   d) at least one control system adapted to control one or more        systems of the equipment assembly;    -   e) optionally, at least one liquid removal system; and    -   f) optionally, at least one packaging system adapted to package        one or more three-dimensionally printed articles.

A build module receives and retains powder deposited thereon by a powderlayering system. In some embodiments, the build module comprises aheight adjustable platform disposed within a cavity in the upper surfaceof the build module, wherein the cavity is defined by sidewalls. Theheight adjustable platform in combination with the sidewalls forms acavity for the powder. The platform can be adapted to raise or lowerincrementally. Powder is placed within the cavity and either directly orindirectly (such as by way of a build plate) onto the platform.

FIGS. 2A-2B depict an exemplary build module (15), wherein FIG. 2A is afront elevation view and FIG. 2B is a perspective side view. The buildmodule comprises a body (16 a), a cavity (16 b) in the upper surface (16d) as defined by the surrounding walls (16 c), and height adjuster (19a, 19 b) engaged with and adapted to raise and lower the heightadjustable platform (17) disposed in the cavity. The build module isdepicted with a build plate (18) disposed above the platform, andengagement (20) by way of which it is engaged with the conveyor system.A build module can be permanently or removably engaged with the conveyorsystem. Although the body and cavity of the build module are depictedhaving a rectangular shape, they can be shaped as needed. The heightadjuster can comprise one or more height adjusters. In some embodiments,the height adjuster is incrementally height adjustable thereby renderingthe height adjustable platform also incrementally height adjustable. Insome embodiments, an incrementally height adjustable component or systemis adapted to raise by one or more increments before and/or afterplacement of a layer of powder on a build module and prior to placementof a subsequent layer of powder the build module.

The height of an increment (thus the thickness of an incremental layer)can be controlled in different ways. In some embodiments, the heightadjuster is computer controlled, whereby the computer controls raisingor lowering of the height adjusting means by the size of an incrementand/or by the number of increments. The size (vertical displacement) ofan increment can vary from incremental layer to incremental layer, bethe same from incremental layer to incremental layer or a combinationthereof. In some embodiments, the size of the increment is the same foreach incremental layer (build lap) of a build cycle, is different forone or more incremental layers of a build cycle, or a combinationthereof.

The size of a vertical increment can be relative to a prior initialposition of the build platform or the height adjuster of the powder fillhead or both. For example, the platform is lowered within the cavity bya first increment to a first position relative to upper surface of thebuild module. A printed incremental layer is formed on the platform atthe first position during a first build lap. The platform is thenlowered by a second increment to a second position but relative to whereit was at the first position. Another printed incremental layer isformed on the platform while at the second position during a secondbuild lap. This process is repeated until completion of a build cycle.

The size of a vertical increment can be relative to one or more absolutepositions of the platform in the cavity of a build module. For example,the build module can comprise plural encoders distributed verticallywithin or adjacent the cavity. The size of a first vertical increment,then, is defined by the absolute position (absolute vertical distance)of the platform with respect to a first encoder. When the platform islowered by a second increment to a target second vertical position,which is determined according to or defined by the absolute verticaldistance of the platform with respect to a second decoder. This type ofabsolute positioning can be exemplified as follows. If the targetincrement is 0.50 mm below the upper surface of a build module, theplatform is commanded to drop 0.50 mm. If the next target increment isto be an additional 0.25 mm, then the platform is commanded to drop to adepth of 0.75 mm below the upper surface of the build module rather thanto command it to drop by 0.25 mm relative to the initial 0.5 mmincrement. This approach is generally superior to using relative moves(0.500, then 0.250) as any minor positioning errors will be resolved orat least not accumulate.

The build plate is adapted to fit within the upper cavity of a buildmodule and to superpose a height adjustable platform within the cavity.The build plate receives and supports a powder bed and/or incrementalpowder layer(s). In some embodiments, the removable build plate is flat,porous, perforated, textured, coated, knurled, smooth or a combinationthereof. Any regular and/or irregular geometric pattern for thearrangement of perforations can be used. The shape of the build platecan be varied as needed. FIG. 6 depicts build plates (40 a-40 h) shapedas a rectangle with rounded corners (40 a), octagon (40 b), cross (40c), circle (40 d), hexagon (40 e), pentagon (40 f),half-rectangle/half-circle (40 g, bullet-shaped profile), rectangle withone concave end and one convex end (40 h); however, any other shape canbe used. The porosity (extent of perforation) of a build plate can beadapted as need to improve operation and manufacture. The build plate(40 a) comprises plural evenly spaced perforations. The build plate (40b) comprises a lattice-type structure or mesh. The build plate (40 f)comprises a rough surface with plural perforations. The build plate (40g). A build plate can be made of any material durable enough towithstand three-dimensional printing thereon. In some embodiments, thebuild plate is adapted for single use or repeated use. In someembodiments, the build plate comprises pressboard, paperboard,cardboard, cardstock, metal, rubber, plastic, silicone, Teflon (PVDF),coated metal, vinyl, nylon, polyethylene, polypropylene, thermoplasticor a combination thereof.

The optional build plate loading system is adapted to reload buildplates onto the build modules engaged with the conveyor. In someembodiments, the build plate loading system is adapted to place one ormore build plates on the height adjustable platform(s) of the one ormore build modules. The build plate loading system (9) depicted in FIGS.7A and 7B comprises a horizontally-telescopic arm (41) pivotally engaged(43) with a vertically-telescopic post (42) and a tray-loading arm (44).The system (9) engages a build plate by a grasp comprised with thevertical tray loading arm (44). The exemplary grasp comprises a plate(46) and an actuatable member (45) that biases/presses a build plateagainst the plate thereby grasping and temporarily retaining the tray.Other grasps can be used to engage and temporarily retain the tray. Insome embodiments, the build plate loading system is a vacuum-basedtransfer system. The build plate system can also be absent, in whichcase build plates can be loaded manually onto the build modules.

The powder-layering system (3) depicted in FIGS. 8A-8C is mounted on asupport (table, frame, body, 54) and comprises at least one powder fillhead (51), at least one powder reservoir (50) and at least one powderfeeder tube (52) driven by a powder feeder drive (53) and adapted totransfer powder from the powder reservoir to the powder fill head. Thepowder feeder tube can comprise a drive motor and screw-type shaft, e.g.an auger or shaft with spiral blades/vanes, such as found in a Schenkfeeder. The powder-layering system forms the incremental powder layerwhen a build module passes through the powder dispensing region (55,also referred to as a layering region), for example in the direction ofArrow J (FIG. 8C).

In some embodiments, a powder fill head (51) depicted in FIG. 9comprises a powder fill head body (60, box), at least one powder fillhead hopper (61) and at least one powder spreader (64). The hopperreceives material from the powder feeder tube to form a temporary supply(63) of powder, which is optionally agitated by powder fill headagitator (62), which can be a powder fill head distribution plateinstead. In some embodiments, the hopper (61) is replaced with a chute(not shown, or distribution plate) having a channeled interior surfacethat distributes powder evenly across the width of the surface anddownward onto a build module. Powder exits the hopper (or chute whichdoes not accumulate a substantial amount of powder) in the direction ofArrow K. In some embodiments, the powder fill head further comprises atleast one powder-height controller adapted to control the relativedistance between the powder spreader (64) and a surface (such as thebuild plate, the upper surface of the build module, the heightadjustable platform, or a prior powder layer) below the powder spreader.An optional distribution bar (or plate, not shown) can be placed betweenthe outlet of the fill head body and the powder spreader (roller). Thedistribution bar serves to better distribute powder across a layer ofpowder prior to being contacted by the powder spreader, whereby anincremental powder layer (65) is formed.

The powder-height controller can raise or lower the powder spreader soas increase or decrease the thickness of a layer of powder placed ontothe platform or a prior layer of powder on the platform. For example, ifthe platform is lowered by a first increment and the powder-heightcontroller is raised by the same or another second increment, then thethickness of powder laid down will approximate the sum of the first andsecond increments. If the platform is lowered by a first increment andthe powder-height controller is lower by a second increment, then thethickness of powder laid down will approximate the difference of thefirst increment minus the second increment. Alternatively, the powderspreader in combination with the powder-height controller can cooperateto compress a layer of powder that has been previously laid down. Thiscan be accomplished by first laying down a layer of powder having afirst thickness during a first build lap, lowering the powder-heightcontroller and powder spreader and then passing the layer of powderunder the lowered powder spreader thereby compressing the layer ofpowder.

In some embodiments, the powder spreader is a cylindrical roller theaxis of which has a radial direction of motion opposite the lineardirection of motion of a build module through the powder layeringsystem. For example, the surface of the cylinder (64) has a lineardirection (Arrow M) opposite the direction (Arrow J) of which anunderlying build module (10) passes under the cylinder. In someembodiments, the powder spreader is a cylindrical roller, bar, rod,plate or straight smooth edge. Powder fill heads of other constructioncan be used.

The amount or rate of powder discharged from the powder fill head can beregulated with one or more controls. A powder discharge feedbackcontroller can monitor the accumulation of powder at the powder spreaderas the powder is being discharged from the powder fill head and spreadto form an incremental powder layer. If the rate at which powder isreleased is too fast, an excessive amount of powder will accumulate atthe powder spreader possibly causing it to spread the powder improperly.The feedback controller then sends a signal thereby causing the rate ofpowder discharge from the powder fill head to decrease. Conversely, ifthe feedback controller senses that the rate of powder discharge is tooslow, it sends a signal thereby causing the rate of powder discharge toincrease. The feedback controller can employ one or more visual, laser,acoustic or mechanical sensors or a combination thereof.

FIGS. 2C-2D depict a portion of a modular (segmented) conveyor system(21) comprising plural conveyor modules (segments, links) (22) andcorresponding engagement means (23) adapted to engage adjacent conveyormodules to each other. FIG. 2C is a front elevation view, and FIG. 2D isa top plan view. A conveyor module comprises a body (22 a), femaleengagement means (22 d), male engagement means (22 c), and one or morebuild module engagement means (22 b) adapted to removably or permanentlyengage build modules. In this exemplary embodiment, adjacent segments(22) pivotally engaged by means of engagement means (23) and pin (22 e)such that the segments can pivot about the axis of the pin (22 e) in thedirection of Arrow LX. Although engagement means (23) is depicted as ahinge-type joint, other engagements can be used.

The equipment assembly (1) optionally comprises one or more powderrecovery systems. The powder recovery system (11) depicted in FIG. 1 andFIG. 2E is optional and is a vacuum-based system comprising a body (11a), aspirator bar (11 c), vacuum source (11 b), and one or more airinlets (11 d, 11 e) adapted to remove powder from one or more surfacesof a build module. In some embodiments, the powder recovery system isadapted to remove loose powder from the upper surface of a build module.The powder recovery system (11) can comprise engagement (11 f) by way ofwhich it is removably or permanently engaged to a surface or support.Additional powder recovery systems are described herein.

FIGS. 3A-3C depict an exemplary printing system (4) adapted to applyliquid to a powder in the printing region of a printing system. FIG. 3Ais a top plan view, FIG. 3B is a side elevation view and FIG. 3C is afront elevation view. In some embodiments, the liquid is appliedaccording to a Cartesian coordinate system instead of a polar coordinatesystem (radial system, cylindrical coordinate system, circularcoordinate system, or spherical coordinate system). In some embodiments,the invention excludes a printing system adapted to apply liquid to thepowder according to a polar coordinate system. An exemplary printingsystem comprises at least one print head (28) that deposits liquid ontoan incremental layer of powder in a build module and at least one liquidfeed system (28 b) that conducts liquid from one or more liquidreservoirs (28 c) to the at least one print head (28). In someembodiments, the printing system comprises plural print heads, pluralliquid feed systems, plural reservoirs or a combination thereof. In someembodiments, the printing system comprises a single print head, pluralliquid feed systems, and plural reservoirs.

The print head of FIG. 3B directs a stream of droplets of liquid into aprinting region (29) through which build modules pass. The exemplarysystem (4) comprises a frame or gantry (tracks 27 a, 27 b) by way ofwhich the print head (28) can translate/move in the direction of ArrowD, which is transverse to the direction of motion of a build moduleduring printing. Translation of the print head can be performed manuallyor via computer controlled operation. In some embodiments, the printhead is stationary when applying liquid onto an incremental layer ofpowder, meaning that as liquid is being applied to a powder layer duringa print lap, the print head (in particular the print modules) does notmove in a direction which is transverse, with respect to the buildplane, to the direction of motion of a build module during printing,i.e. during the application of liquid. Such a means of printing isdifferent than prior systems wherein the print head (in particular theprint module(s)) moves back and forth, in a direction which istransverse to the direction of motion of a build module, duringprinting.

A print head can comprise one or more print modules that deposit theliquid onto a layer of powder. The print head (28) of FIG. 3C comprisesfour print modules that form corresponding printing regions (29 a-29 d).When a print head comprises plural print modules, the arrangement/layoutof the print modules can be as needed. The print head (30) of FIG. 4comprises plural print modules (4) arranged in plural columns with eachcolumn comprising plural print modules. A powder can pass across theprint modules in the direction of Arrow E such that print direction istransverse to the horizontal shape of the print module.

Other suitable arrangements for the print modules are depicted in FIG.5. The print head (34) comprises a single print module. The print head(35) comprises four print modules pared in groups (35 a, 35 b) of twooffset horizontally from one another. The print head (33) is somewhatsimilar to head (35) except that the print modules (35 a, 35 b) arewider horizontally and offset to a greater extent horizontally than arethe print modules (33 a); moreover, the print modules are horizontallyoffset from one another. The print head (32) comprises two linearly andtransversely offset groups (32 a, 32 b) of print modules. When viewed inthe direction of Arrow E, the adjacent edges of the two groups overlap(each group overlaps the dashed line).

By offsetting the print modules as depicted for module (33), theapparent overall print resolution of the print head can be increased.The print modules can be offset in staggered, interlaced, sobered, orangled arrangements relative to the print head in order to increaseoverall print density/resolution. For example, if the print resolutionof each print module is 75 dpi (drops per inch), then the apparentoverall print resolution of the print head (33) can be 75 dpi, 150 dpi,225 dpi, 300 dpi, 375 dpi, 450 dpi or even higher. If the printresolution of each print modules is 100 dpi, then the apparent overallprint resolution of the print head (33) can be 100 dpi, 200 dpi, 300dpi, 400 dpi or even higher. In some embodiments, the print resolutionof the print head is the same as or greater than the print resolution ofa print module comprised within the print head. In some embodiments, theprint resolution of the print head is a multiple of the print resolutionof one or more print modules comprised within the print head. In someembodiments, the print resolution of the print head is the less than theprint resolution of a print module comprised within the print head.

The arrangement of one or more print modules in the print head can bemodified as needed to provide the desired printing result. FIG. 16depicts a partial print station comprising a powder fill head (176) anda print head (178) below which is a build module (175) moving in thedirection of Arrow Q through a powder dispensing region and a printingregion, respectively. The fill head, which is disposed transverse to thedirection of motion of the build module, remains transversely andlongitudinally stationary (with respect to the plane defining the uppersurface of the build module, even though it can move vertically towardor away from said plane) as it places an incremental layer of powderonto and across the width of a cavity of the build module. The buildmodule and incremental layer of unprinted powder moves in the directionof Arrow Q, whereby they pass through the printing region beneath theprint module, which is disposed transverse to the direction of motion ofthe build module. The print module remains transversely, longitudinallyand vertically stationary with respect to the plane defining the uppersurface of the build module. The print module applies liquid onto theincremental layer of powder according to a predetermined pattern,thereby forming an incremental printed layer (180) comprising article(s)181. The exemplary print head comprises a single print module (179;depicted in dashed line) that spans the width of a cavity of the buildmodule.

The print head (185) depicted in FIG. 17A comprises four print modules(186) arranged in both transverse and longitudinal displacement (withrespect to the direction of motion of the print head). Together the fourprint modules span the width of the cavity of the build module. Theembodiment (187) of FIG. 17B differs from that of FIG. 17A in that thefour print modules (188) are only transversely displaced but notlongitudinally displaced.

In some embodiments, the one or more print heads is/are stationary whenapplying liquid onto an incremental layer, i.e. when printing. The oneor more print heads can, in particular, be transversely andlongitudinally stationary, with respect to the linear direction ofmotion of a build module (and thus an incremental layer of powder), whenprinting. Particular embodiments include those wherein: a) the printingis performed according to a Cartesian coordinate algorithm; b) the buildmodule moves during printing in a linear direction that is perpendicularto the disposition of the print module (and one or more print heads); c)the print head and one or more print modules are stationary whenprinting (when applying liquid to an incremental layer of powder) and donot move in a direction that is transverse or longitudinal with respectto the direction of motion of the build module; and/or d) printing isnot performed solely according to a polar coordinate algorithm.

The three-dimensional printing system/assembly of the invention employsCartesian coordinate based printing system and algorithms. Unlike othersystems that move the print heads transversely and/or longitudinallywhen printing, the print heads of the invention are substantiallystationary during printing. The term “transversely” is determined inrelation to the direction of motion of a build module beneath a printhead and means substantially perpendicular to the direction in which abuild module is conducted through a printing area. The term“longitudinally” is determined in relation to the direction of motion ofa build module beneath a print head and means substantially parallel tothe direction in which a build module is conducted through a printingarea. Application of liquid across the width of powder layer beneath aprint head is accomplished by employing one or more print modules thatindividually or together traverse at least 75%, 80%, at least 85%, atleast 90%, at least 95%, at least 97.5% or at least 99% the width of thepowder layer. In the present case, the “width” of the powder layer isdetermined along a direction transverse to the direction of motion of abuild module beneath a print head, and the term “length” is determinedalong a direction parallel to the direction of motion of a build modulebeneath a print head. In other words, a single print head can traversethe width or plural print heads transversely adjacent to each other cantraverse the width of the powder layer.

In particular embodiments, the print head comprises plural print modulesthat individually do not but together do span the width of anincremental powder layer and/or of the cavity of a build module. In someembodiments, one or more print modules together modules span at least50%, at least 55%, at least 75%, at least 90%, at least 95%, at least99% or all of the width of the cavity of the build module. In particularembodiments, the build module moves in a first direction, and the printhead is stationary when liquid is being applied to the incrementalpowder layer. In particular embodiments, printing is performed primarilyor solely according to a Cartesian coordinate algorithm. For example,the algorithm controls application of the droplets of the printing fluidrelative to the linear (non-radial, straight) direction of the conveyorsuch that the print head applies droplets in a direction that isparallel (longitudinal) or is perpendicular (transverse) with respect tothe linear direction of motion of the conveyor. The conveyor andcorresponding build modules only move in a straight linear directionbeneath the print head and build head.

An alternate embodiment of the invention is depicted in FIG. 17C,wherein the print head (189 a) comprises one or more or plural printmodules that do not span the width of an incremental powder layer and/orof the cavity of a build module. This print head is either stationarywhen printing (when applying liquid to an incremental layer of powder)or moves transversely, with respect to the direction of motion of thebuild module, while applying liquid to the powder. The print modules ofthe print heads (32, 33, 35, 189 a, 189 b of FIGS. 5 and 17C) arearranged such that the jets on multiple print heads are interleaved toincrease the print density across the print bed. For example, individualprint modules having a native print density of 100 dpi are interleavedtogether such that four of the print heads together provide a 400 dpiprint density.

In some embodiments, clusters of print modules, such as depicted in 17D,are arranged so their overall span covers only part of the width of apowder layer, such that plural print heads (each containing a cluster ofprint modules with interleaved jets) are required to cover the fullwidth of the powder layer. For example, three print heads (189 b), eachhaving a cluster of print modules which together spans only 2.5″, wouldneed to be arranged in a horizontally offset manner in order to coverthe width of a powder bed or layer that is between 5 to 7.5 inches wide.

The at least one printing system can apply liquid according to anypredetermined print pattern or randomly onto an incremental layer ofpowder. The pattern can be the same from incremental layer toincremental layer or can be different for one or more incremental layersof a printed article. Generally, two adjacent print patterns willcomprise at least two overlapping printed portions such that at least aportion of the printed/bound powder in one printed incremental layerwill adhere (be bound) to at least a portion of the printed/bound powderof an adjacent printed incremental layer. In this manner, plural stackedadjacent printed incremental layers adhere to each other thereby forminga three-dimensionally printed article comprising plural adjacent printedincremental layers of completely or partially bound powder. Even thougha three-dimensionally printed article can include undercuts, overhangs,cavities, holes and other such features, at least part of the printedportions of adjacent printed incremental layers must adhere to oneanother in order to form and fill the composite volume of the article.

The printing system employs a Cartesian coordinate-based printingalgorithm when applying liquid to an incremental powder layer. Thesystem includes a computer and associated software that comprises one ormore print jobs. A print job includes, among other things, informationon the thickness of incremental layers and the predetermined pattern tobe printed on the incremental layers of a printed article. The print jobprovides layer-by-layer instructions to the print head (print module(s))about the creation and placement of droplets of liquid onto theincremental powder layer. The print job is based upon the series oftwo-dimensional images (slices) that, when stacked, together form apredetermined three-dimensional image (object).

Without being held bound to a particular mechanism, a targetthree-dimensional article is designed, such as with a CAD program. Avirtual image of the target article is sliced virtually into pluralstacked thinly-sliced images (which are referred to herein as“two-dimensional” images), wherein each two-dimensional image isactually the thickness of an incremental powder layer. The sum total ofthicknesses of the image slices equals the total “height” of a targetarticle. Each two-dimensional “image” is then converted into a subset ofprinting instructions, which together define a predetermined printingpattern for that image. All of the subsets of printing instructions arejoined together to form a final set of printing instructions that areused by the computer to control printing. Aside from incremental layerthickness, two-dimensional shape of predetermined patterns, and shape oftarget article, the final set of print instructions also includesspecification of or consideration of linear speed of the build modulebeneath the print head, rate of application of liquid to incrementalpowder layers, length and width of the incremental powder layer,dimensions of the cavity of a build module, incremental heightadjustment of the height adjustable platform of the build module, rateof loading of powder into the powder fill head, rate of loading ofpowder into a build module to form an incremental layer, rate oftransfer of powder from a feed reservoir to the fill head, resolution ofthe two dimensional image to be printed on each incremental layer, thenumber of applications of liquid to each incremental layer, applicationof one or more specific liquids to one or more specific locations of theincremental layer, starting and stopping of liquid application withrespect to each build module, the number of articles to be printed, thenumber of build modules in the equipment assembly, the number of buildmodules to be printed upon, rate at which the platform of the buildmodule moves down, timing for starting and stopping powder deliveryrelative to the entire build cycle, rotational speed of leveling device(roller) and other such parameters.

An equipment assembly comprises a control system comprising one or morecontrollers. Without being held bound to a particular mechanism, ahoming switch located at a fixed point of the conveyor (FIG. 1) providesa reference point as to the location of the “first” build module in agroup of build modules. From there, a computer is able to determine thelocation of the rest of the build modules in that group by knowing thesize of the conveyor, the spacing of the build modules and thedimensions of the build modules. The control system can also comprise aproximity sensor that specifies the location of one or more buildmodules relative to the conveyor. The control system comprises asynchronizer that facilitates synchronization of operation of thevarious components of the equipment assembly. By taking intoconsideration the track (linear) speed of the conveyor and the targetthickness and width of an incremental layer, a computer is able toinstruct the powder layering system to charge powder onto the buildmodules at a certain feed rate. After part of a lap or after one or twocalibration laps, the powder feed rate can be continuous. Once a properincremental powder layer is formed, deposition of liquid onto theincremental layer can begin. A proximity sensor senses the leading edgeof a build module and then sends instruction to the print system. Acomputer controlling the print system takes into consideration a set ofprinting instructions (which can include among other things the targetprint resolution (density), the image(s) (pattern(s)) to be printed onthe incremental layer, the target rate of liquid deposition, the numberof liquids to be deposited, the dimension of the print head and printmodules, track speed, the set of images (patterns) that are to beprinted to form a target 3D printed article, target article porosity ordensity, or other such parameters) and the signal generated by a wheelencoder, for example, to provide a pulse that sets the print rate atwhich to consume the image files in the printing instructions and theresolution at which to print the image file(s). Following completion oflayering and printing per the printing instructions, a build cycle iscompleted.

As described herein, the powder system can comprise one or more feedbackcontrollers that determine the proper powder feed rate into a powderfeeder and into the build modules. Likewise, the printing system cancomprise one or more feedback controllers that determine the rate atwhich printing fluid (liquid) is being applied and/or consumed and cantherefore control the liquid application rate and can also the reloadingof liquid reservoir(s).

A liquid removal system, such as a dryer, can comprise one or morerelative humidity controllers, temperature controllers and conveyorspeed controllers. The system is therefore capable of adjusting dryingtime and conditions to provide printed articles containing the desiredlevel of moisture.

In some embodiments, one or more components of the equipment assemblyare computer controlled. A controller is independently selected at eachoccurrence from a computerized controller, electronic controller,mechanical controller or a combination thereof. In some embodiments, thecontrol system comprises one or more computerized controllers, one ormore computers, one or more user interfaces for one or more computers.In some embodiments, one or more components of the three-dimensionalprinting build system are computer controlled. In some embodiments, theconveyor system, the height adjustable platforms of the build modules,the at least one powder layering system and the at least one printingsystem are computer controlled. In some embodiments, the equipmentassembly is adapted to spread layers of powder and print droplets ofliquid in a predetermined pattern according to instructions provided bya computerized controller. In some embodiments, the predeterminedpattern is based on one or more two-dimensional image files comprisingpixels. In some embodiments, the two-dimensional image files arestructured such that certain pixels indicate dispensing of droplets, andother pixels represent no dispensing of droplets. In some embodiments,the two-dimensional image files include different colors of pixels toindicate dispensing of different liquids, or no dispensing of liquid.

FIGS. 19A-19C, depict a flow chart for operation of an exemplaryembodiment of the invention. The process is initiated, e.g. by anoperator or electronic component such as a computer. An operatoractivates and checks the status of system and assembly components, whichare then synchronized, after which time the system (assembly) is readyfor operation. Printing fluid and powder are loaded into theirrespective systems as required of the product to be three-dimensionallyprinted. Build plates are loaded into build modules and a build cycle isinitiated. The level of printing fluid(s) and powder(s) are checked andwhen the required amount is present, conveyor operation is initiated.Moving to FIG. 19B, the powder feed rate and transport speed (conveyorspeed) for the build module is applied and a query is made to determinewhether or not a build module is supposed to receive powder. If so, theplatform is lowered and a layer of powder is deposited onto the buildmodule as it passes under the powder fill head. If not, the build moduledoes not receive powder. A query is then made to determine whether ornot the powder layer is supposed to receive a printed image. If so, atwo-dimensional pattern is printed onto the layer as the build modulepasses under the print head. If not, the build module does not receiveprinting solution. A query is made to determine whether or not all ofthe build modules mounted on the conveyor have been processed, i.e.whether or not the build lap is completed or whether or not the buildmodule is supposed to receive another layer of powder. If not, anyunprocessed build module is processed. If all of the build modules havebeen processed, i.e. the build lap is complete, a query is made todetermine whether or not a build cycle is complete. If not, one or moreadditional build laps are conducted. If so, the build modules areprepared for unloading of build plates as described in FIG. 19C.Completed build plates that bear three-dimensionally printed powder bedare unloaded and transferred to drying trays. After a build plate hasbeen removed from a build module, another build tray is placed in theempty build module. After all build plates have been unloaded, a queryis made according to FIG. 19A to determine whether or not additionalbuild cycles will be conducted. If not, the process is terminated. Ifso, the next build cycle process is initiated.

FIG. 20 depicts an exemplary subroutine detailing how the platform layerincrement is controlled within a build lap and a build cycle. In thisexample, the layer thickness (increment) is provided by a productdefinition. A cumulative thickness is calculated according to the numberof powder layers already laid down. The platform is dropped to thecalculated thickness and a determination is made to confirm that it isat the correct position within a predefined tolerance. A query is thenmade to determine whether or not the platform of all the build modulesin a particular build lap have dropped to the correct position. If not,the platforms are adjusted as required. If so, a query is made todetermine whether or not all layers of a build cycle are complete. Ifso, the build plates are unloaded as described herein. If not, theprocess of this figure is repeated for each of the build layers asneeded until the build cycle is complete.

FIG. 21 describes an exemplary subroutine detailing operation of theprinting system. A build process is initiated and the necessaryamount(s) of printing fluid is loaded into the reservoir(s). A set ofimage files are identified and conveyor operation is begun. Duringoperation, the level of printing fluid(s) is monitored so that it can bereplenished as needed. When a build module passes beneath a printhead, atrigger signal is generated prompting a query to determine whether ornot the build module is to receive a printed image. If not, the triggersignal is ignored. If so, an print image file is received and processedsuch that the columns of image pixels (pixels that are aligned along theaxis of movement of the build module) are assigned to specific jets ofthe printhead. In addition, rows of image pixels are sent to theprinthead taking into consideration the linear speed of the conveyor andthe intended print density of the image to be printed. The printheadthen delivers printing fluid droplets, as per the printing instructions,to the powder layer on a build module. A query is then made to determinewhether or not all build modules have been processed. This query can berepeated for the build lap and/or build cycle level. Upon completion ofa build cycle, the process can be terminated. If needed, the printheadcan be retracted and cleaned.

FIG. 22 depicts a flow chart of an exemplary process for designing adosage form and determining the layer thickness thereof and image files(two-dimensional printing patterns) there for. The process can beconducted with or without a computer. A dosage form having a specifiedthree-dimensional structure and comprising a target dose of drug isdesigned. The approximate target powder layer thickness is selected andthe height of the dosage form is divided by the target incrementalpowder layer thickness to provide the number of powder layers requiredto prepare the dosage form. Based upon the layer and its location withinthe dosage form, each layer is assigned as needed an initialtwo-dimensional pattern, i.e. an image file, which ultimately results ina set of printing instructions employed by the printing system to createa corresponding printed increment layer. The image file assigned to eachlayer can be input, or it can be retrieved from an image library. Inorder to determine whether or not archived images from the image libraryare required, the system queries whether or not all layers have beenassigned an image file as needed. If so, the design of the dosage formis complete and the process is terminated. If not, the system querieswhether or not the image required for a specific layer exists in theimage library. If so, the image file is retrieved from the library andassigned to the respective powder layer. The system then again querieswhether or not all layers have been assigned an image file as needed andthe loop of logic continues as needed until completion of design of thedosage form. If the image file is not present in the image library, anew image file is created, optionally stored in the image library, andassigned to the respective layer, and the loop of logic continues asneeded until completion of the dosage form design. It should beunderstood that one or more layers might not require any image file atall, meaning that specific layer would not be printed during preparationof the dosage form.

The equipment assembly of the invention can comprise one or more bedtransfer systems adapted to transfer three-dimensionally printed beds,one or more at a time, away from the three-dimensional printing buildsystem. FIG. 10A is a top plan view and FIG. 10B is a side elevationview of an exemplary bed transfer (unloading) system (8) comprising aframe (70), receiving platform (76), tray-loading platform (77), and bedtransfer mechanism (71) moveably engaged with the frame and superposinga bed-transferring region (75). The bed transfer mechanism (71)comprises mounts (71 c) adapted to translate along tracks (72 a, 72 b)in the direction of Arrow N in a reciprocating manner. The bed transfermechanism also comprises a receptacle (71 a) comprising a cavity (82)adapted to receive and temporarily retain a three-dimensionally printedbed (83) having an optional build plate (10). In an alternateembodiment, the receptacle is a push plate or U-shaped coral (71 d)comprising a receiving area adapted to receive and temporarily retain athree-dimensionally printed bed. The receptacle (71 a) reciprocates in avertical manner in the direction of the Arrow P by means of reciprocator(71 b) engaged with the receptacle (71 a) and the body (71 d) of the bedtransfer mechanism (71). During operation, a conveyor conducts andpositions a build module (7 a) beneath the receptacle (71 a) and in thebed-transferring region (75) so as to align the three-dimensionallyprinted bed (83) and build plate with the cavity (82). The receptaclethen lowers in the direction of Arrow P an amount sufficient to retainsubstantially all of the three-dimensionally printed bed and build platewithin the cavity. The bed transfer mechanism (71) thenslides/translates the printed bed and build plate in the direction ofthe Arrow N onto the receiving platform (76) and then onto a transporttray (74). The receptacle is then raised in the direction of the Arrow Pleaving the printed bed and build plate on the transport tray andtranslates back in the direction of Arrow N to the original positionsuperposing a build module. The transport tray (74) is then conducted inthe direction of the Arrow B.

FIG. 10C depicts an alternate embodiment of a bed transfer systemcomprising a diverter (84) and a conveyor (86). The diverter directsbuild modules or build plates comprising printed beds (87) from theconveyor (85) of the build system onto an adjoining conveyor (86), whichoptionally transfers the printed beds to a liquid removal system orother downstream processing apparatus (not shown). The diverter can beadapted to raise and lower. In a first position, it does not directprinted beds away from the build system and in a second position itdoes.

In some embodiments, the bed transfer system is adapted to transferthree-dimensionally printed beds to one or more liquid removal systems,one or more harvesting systems and/or one or more packaging systems. Insome embodiments, the transfer system is integrated with the conveyorsystem, the liquid removal system or both.

A liquid removal system is adapted to receive one or more build plates(containing a printed bed) and to remove liquid from one or more printedpowder layers onto which the liquid has been applied and/or from thethree-dimensionally printed bed. A liquid removal system can be aprocess area through which one or more of the build modules areconducted. For example, the liquid removal system in FIG. 1 can be theprocess area over the conveyor and excluding the region under theprinting region. Alternatively, a liquid removal system can be anotherprocess area not directly associated with the three-dimensional printingbuild system, such as a temporary retaining or storage area whereinthree-dimensionally printed beds are placed and dried under ambientconditions. In some embodiments, a liquid removal system is one or moredryers.

FIGS. 13A-13B depict exemplary liquid removal systems. FIG. 13A is apartial sectional side elevation view of a dryer (130) adapted to removeor reduce the amount of liquid in a three-dimensionally printed bed (83)or article. The dryer comprises a housing (131) within which arecontained plural heating elements (137), a conveyor system (138) and onemore exhaust ports (132). The housing comprises an inlet (133) and anoutlet (134) through which three-dimensionally printed beds (orarticles) and their respective build plates are conducted by way ofconveyors (135, 136, respectively). During operation, the printed bedsare conducted through the inlet (133) and carried by the conveyor system(138) through a predetermined path as they are exposed to the heatingelements (137), which affect evaporation of liquid from the printedbeds. When the printed beds (or articles) exit the dryer, they compriseless liquid than they did when they entered the dryer. Although notdepicted in FIG. 13A, the dryer can comprise a vacuum system adapted toreduce the pressure within the dryer or air-handling system adapted toincrease or otherwise control the flow of air through the dryer.Although the path of the conveyors is depicted as “S-shaped” in FIG.13A, the path can instead be any path desired, e.g. U-shaped, Z-shaped,N-shaped, n-shaped, O-shaped, etc.

FIG. 13B depicts an alternate embodiment of a dryer (141) suitable as aliquid removal system. The dryer comprises a housing (142), within whichare contained plural heating elements (146) and a conveyor system (145).The housing comprises an inlet (143) and an outlet (144) through whichthree-dimensionally printed beds and their respective build plates areconducted by way of the conveyor. In some embodiments, the dryercomprises one or more covers (147) for the inlet and/or outlet.

In some embodiments, the three-dimensionally printed bed comprises loosepowder and one or more three-dimensionally printed articles. Anequipment assembly of the invention can further comprise one or moreharvesting systems adapted to separate loose powder from the one or morethree-dimensionally printed articles. In some embodiments, the harvesterprocesses build plates already processed by the liquid removal system.In some embodiments, the harvester comprises loose powder collectionmeans and three-dimensionally printed article collection means. In someembodiments, the harvester comprises a vibrating and/or orbiting surfaceadapted to receive the three-dimensionally printed bed. In someembodiments, the harvester comprises one or more deagglomerators.

In some embodiments, the equipment assembly further comprises one ormore dedusters adapted to remove loose powder from articles that havebeen harvested. In some embodiments, a deduster comprises one or moreair brushes.

The exemplary combination harvester and deduster system (150) depictedin side elevation view in FIG. 14 comprises a frame (151), a receivingplatform having an air-dispenser (161), bed transfer mechanism (152)moveably engaged with the frame and superposing a bed transfer region,aspirator (154), deagglomerator (156), deduster (157), printed articlecollector (158), and powder collector (159). The also comprises at leastone air brush (161). The bed transfer mechanism (152) comprises mountsadapted to translate along tracks (153) in the direction of Arrow N in areciprocating manner. The bed transfer mechanism also comprises areceptacle (167) comprising a cavity (166) adapted to receive andtemporarily retain a three-dimensionally printed bed (83) having anoptional build plate (10). The receptacle (167) reciprocates in avertical manner by means of reciprocator engaged with the receptacle andthe body of the bed transfer mechanism (152). During operation, aconveyor (155) conducts and positions a printed bed (83), build plate(10) and transport tray (74) beneath the receptacle (167) and in a bedtransfer region so as to align the three-dimensionally printed bed,build plate and transport tray with the cavity (166). The receptaclethen lowers onto the transport tray an amount sufficient to retainsubstantially all of the three-dimensionally printed bed within thecavity. An aspirator (154) then aspirates the printed bed (83) by way ofa conduit (165) and a perforated plate in the cavity and above the bed,thereby removing a major portion of the loose powder contained withinthe bed while leaving behind one or more printed articles (160) withinthe cavity of the receptacle. The bed transfer mechanism (152) thenslides/translates the printed bed and build plate in the direction ofthe Arrow N over one or more airbrushes (161) adapted to direct a flowof air at the printed articles in the cavity to assist in releasingadditional loose powder from the printed article(s). The empty buildplate (10) and transport tray (74) are conveyed away from thebed-transferring region. A powder collector (159) is adapted to receiveloose powder and other solid material not otherwise collected by theaspirator (154). The bed transfer mechanism continues to move in thedirection of the Arrow B until it superposes a deagglomerator (156). Theaspirator is then turned off and the printed particles fall onto of theprocess tray of the deagglomerator, which is adapted to remove andcollect agglomerates from the printed article(s) to providedeagglomerated printed articles (162). The bed transfer mechanism (152)then returns to its original position in preparation of loading andprocessing of additional printed beds.

The process tray of the deagglomerator vibrates (and/or orbits) andconducts the printed articles in the direction of Arrow B toward thededuster (157) while degglomerating the printed particles. The dedusteralso comprises a vibrating process tray adapted to remove and collectdust from the deagglomerated printed articles to provide dedustedprinted articles (163). The finished printed articles (164) areconducted to a printed article collector (158). The deduster and/ordeagglomerator can further comprise solids collector for collectingloose powder and/or agglomerates.

FIG. 18 depicts an exemplary harvester system (190) and a dedustersystem (200). The harvester system comprises a housing (191), areceptacle (192), a vibrating surface (193) within the receptacle and anoutlet (194) for the receptacle. A perforated build plate below a dryprinted bed (loose powder and printed article) is placed on thevibrating surface. Loose powder is dislodged from the printed bed as thesurface vibrates. The recovered loose powder falls and is collected inthe receptacle, after which it is unloaded from the receptacle throughthe outlet. The recovered loose powder is collected in a container(195). Collection of the loose powder can be done manually, mechanicallyand/or with a vacuum system.

The deduster system (200) of FIG. 18 comprises a housing (201),receptacle (202), drawer (203), enclosure (204), one or more air jets,e.g. air knives, (205, not depicted) within the enclosure, inlet (206,not depicted) for the enclosure, and an outlet (207) for the enclosure.A perforated build tray having one or more printed articles that havebeen harvested is placed in the drawer which is subsequently pushed intothe enclosure by way of the inlet, thereby forming a substantiallyenclosed dedusting area. One or more air jets direct pressurized airtoward the printed article(s), whereby both coarse and fine loose powderthat has clung onto the printed article(s) is dislodged there from. Theloose powder falls into the receptacle and is conducted to the outletalong with the flow of air released by the air jet(s). The dedustedprinted article(s) is (are) are retrieved by opening of the drawer. Therecovered loose powder collected in a container. Collection of the loosepowder can be done manually, mechanically and/or with a vacuum systemand/or air-handling system. The deduster system and/or the harvestersystem can be placed within a larger enclosure (208) to minimizespreading of dust in a process area.

Loose powder, agglomerates or particulates collected during the buildcycle, drying, harvesting, deagglomerating and/or dedusting can bedisposed or can be blended to form recovered bulk material that can bemilled (optionally) and recycled back into a feed supply of virginunprinted bulk material. Such a bulk material recovery system cancomprise one or more vacuum systems, one or more pressurized airsystems, one or more non-vacuum mechanical systems, one or more manualsystems or a combination thereof for transferring bulk material from onelocation to another.

FIGS. 12A-12E depict exemplary generalized layouts for conveyor systemsand build stations of a three-dimensional printing build system. FIG. 2Adepicts a top plan view of a three-dimensional printing build system(105) somewhat similar to the one depicted in FIG. 1. The system (105)comprises a cyclic and iterative conveyor system (110), a first buildstation (111), an optional second build station (115), and plural buildmodules. The plural build modules are conducted through the first buildstation, and optionally the second build station if present, and thenback through the first build station in the direction of the Arrow A.The build station (111) comprises a powder-layering system (112) and aprinting system (114).

FIG. 2B depicts a top plan view of a three-dimensional printing buildsystem (106) comprising a linear conveyor system (118), a first buildstation (111), a second build station (115), and plural build modules.The plural build modules are conducted from position X1 through thefirst build station to position X2 and then through the second buildstation to position X3 in the direction of Arrow A. Further processingof printed articles is done downstream of the build system (106). Insome embodiments, the conveyor system is a linear conveyor system thatconducts build modules from a first build station to a second buildstation and optionally to a third or other build station in a non-cyclicor non-iterative manner.

FIG. 2D depicts a top plan view of a linear and iterativethree-dimensional printing build system (107) comprising a linearconveyor system (119), a first build station (111), an optional secondbuild station (115), and plural build modules. The plural build modulesare conducted from position X1 through the first build station toposition X2 and then through the second build station, if present, toposition X3 and then, in reverse direction in the direction of Arrow AR,back through the second build station, if present, and the first buildstation. A third or more other build stations can be included, and ifpresent, the build modules are conducted through them.

FIG. 12D depicts a top plan view of a linear and iterativethree-dimensional printing build system (108) comprising plural buildstations (111, 115, 126, 127), plural build modules, and build moduletransfer means (124, 125). Empty build modules on a conveyor (120) aretransported from position Z1 to position X1. The conveyor (121) thenconducts build modules consecutively from positions X1 to X2 to X3 andthrough the build stations (111, 115). Build module transfer means (124)then transfer build modules in the direction of Arrow AZ from positionX3 to position X4. A second conveyor then conducts build modulesconsecutively from positions X4 to X5 to X6 and through the buildstations (126, 127, respectively). Build module transfer means (125)then transfer build modules in the direction of Arrow AY from positionX6 to position X1. This type of build lap is repeated as many times asnecessary until the desired printed article is formed and unloaded fromthe printing build system (108) by way of the conveyor (122).

FIG. 12E depicts a side elevation view of a three-dimensional printingbuild system (109) somewhat similar to that of FIG. 12D. In thisembodiment, however, the conveyors (128, 129) are arranged verticallyone above the other rather than side by side. Moreover, the lowerconveyor system (129) does not have a build station specificallyassociated with it.

As noted above, it takes plural build laps to construct athree-dimensionally printed article from a powder bed. FIG. 11A depictsa partial cross-sectional view of a build module (90) comprising a body(91) having an upper surface (91 a) and a height adjustable platform(92) having an upper surface (92 a). The hollow arrows indicate processsteps, whereas the filled-in black arrows indicate direction of motionof the platform in the figure. The build module (90) is depicted instarting position at Stage 0. In process steps A1 and A2, the platformis lowered thereby forming a cavity (93) defined by the inner surface(91 b) of the build module and the upper surface of the platform. Abuild plate (10) is then placed on top of the platform as depicted inStage I. In process step B1, a layer of powder (94) is placed in thecavity and over the build plate such that the position of upper surface(94 a) of the layer substantially matches (or is at the same height of)the position of the upper surface (91 a) of the build module as depictedin Stage II. In process step C1, platform is lowered again by anincrement thereby forming a new cavity (95) above the surface of thepowder layer (94) as depicted in Stage III. In process steps D1 and D2,another layer of powder is placed in the cavity and then printed upon toform one or more sections of bound powder as depicted in Stage IV. Inprocess step E1, the platform is lowered again and another cavity isformed above the previous layer of powder as depicted in Stage V. Inprocess steps F1 and F2, another layer of powder is placed in the cavityand then printed upon to form one or more sections of bound powder asdepicted in Stage VI. The print pattern used in process step D2 issimilar to the print pattern used in process step F2. In process stepG1, the platform is lowered again as depicted in Stage VII. In-processstep H1, a layer of powder is placed in the just formed cavity over theprior layer of powder as depicted in Stage VIII thereby completingformation of a printed bed comprising loose powder (97) and pluralprinted articles (96). In process step J1, the receptacle (71 a) of abed transfer means is placed above the printed bed such that the cavityof the receptacle superposes and is aligned with the printed bed asdepicted in Stage IX. In process step K1, the platform is raised suchthat the build plate and printed bed are disposed within the cavity asdepicted in Stage X. In process step L1, the receptacle istranslated/slid in the direction of Arrow N thereby unloading the buildstray returning it to Stage 0.

The print pattern used for individual print cycles can vary as neededand need not be the same for each build lap. FIG. 11B depicts the buildmodule of the FIG. 11A. The process steps A1, A2, B1 and C1 in FIG. 11Bare similar to those steps in FIG. 11A; however, the process of FIG. 11Bincludes the process step B2 whereby the first layer of powder isprinted upon to form a layer comprising loose powder (100) and boundpowder (101). In process step D1, a layer of powder is placed within thecavity, and in process step D3, the layer is printed upon using a printpattern that is different than the print pattern used in process step B2such that the cross-section of the bound powder (102) in Stage IV ofFIG. 11B is different than the cross-section of the bound powder inStage IV of FIG. 11A. The pattern of step D3, however, overlaps with thepattern of step B2 sufficiently that the resulting printed layers adhereto one another. The platform is lowered again according to process stepE1. Powder is then layered into the cavity in process step F1 andprinted upon in process step F3. Again, the print pattern used inprocess step F3 is different than the print pattern used in processsteps D3 and B2, such that the cross-section of the bound powder (103)in stage VI comprises three different patterns, which patterns aredifferent than those depicted in stage VI of FIG. 11A. The pattern ofstep F3, however, overlaps with the pattern of step D3 sufficiently thatthe resulting printed layers adhere to one another. The platform islowered again according to process step G1 as depicted in stage VII. Inprocess step H1, a layer of powder is placed within the cavity, and inprocess step H2, the layer is printed upon using a print pattern that isdifferent than any of the prior print patterns used such that thecross-section of the bound powder (104) in the printed bed in stage VIIIcomprises six different patterns, which patterns are different thanthose depicted in stage VIII of FIG. 11A. The pattern of step H2,however, overlaps with the pattern of step F3 sufficiently that theresulting printed layers adhere to one another. In process step J1, aperforated plate is placed above the printed bed and a receptacle of abed transport means is placed above the plate as depicted in Stage X. Inprocess step K1, the perforated plate, printed bed and build plate areraised into the cavity of the receptacle. In process step L1, thereceptacle is translated away in the direction of Arrow N leaving behindthe build module in its initial stage 0.

Upon completion of the exemplary print cycle, the three-dimensionallyprinted bed can be further processed as described herein.

Conveyor systems useful for conducting solid articles from one locationto another during manufacture include, by way of example, a modularconveyor, non-modular conveyor, continuous conveyor, contiguousconveyor, conveyor belt, cam, pallet conveyor or link conveyor.Combinations thereof can be used.

FIG. 15 depicts a side elevation view of an exemplary packaging system(170) adapted to package one or more three-dimensionally printedarticles (164). The system comprises a hopper (171) that providesthree-dimensionally printed articles which are placed onto a conveyor(173). The articles are conducted through a packaging module (172) thatplaces one or more articles into a package (174). Suitable packagingsystems can employs bottles, blister packs, tubes, boxes and other suchcontainers.

The various components and systems of the equipment assembly willcomprise parts made of durable materials such as metal, plastic, rubberor a combination thereof. In some embodiments, components of theequipment assembly comprise 304 or 316 stainless steel where possible.

The powder can comprise one or more materials suitable forpharmaceutical or non-pharmaceutical use. In some embodiments, thepowder comprises one or more pharmaceutical excipients, one or morepharmaceutically active agents, or a combination thereof. In someembodiments, the three-dimensionally printed article is a pharmaceuticaldosage form, medical device, medical implant, or other such article asdescribed.

Exemplary types of pharmaceutical excipients that can be included in athree-dimensionally printed article include, by way of example andwithout limitation, chelating agent, preservative, adsorbent, acidifyingagent, alkalizing agent, antifoaming agent, buffering agent, colorant,electrolyte, flavorant, polishing agent, salt, stabilizer, sweeteningagent, tonicity modifier, antiadherent, binder, diluent, directcompression excipient, disintegrant, glidant, lubricant, opaquant,polishing agent, plasticizer, other pharmaceutical excipient, or acombination thereof.

Exemplary types of non-pharmaceutical excipients that can be included ina three-dimensionally printed article include, by way of example andwithout limitation, ash, clay, ceramic, metal, polymer, biologicalmaterial, plastic, inorganic material, salt, other such materials or acombination thereof.

In some embodiments, the powder comprises one or more, two or more,three or more, four or more, five or more, six or more, seven or more,eight or more, nine or more, ten or more or plural components, eachcomponent being independently selected at each occurrence. In someembodiments, the equipment assembly comprises one or more, two or more,three or more, four or more, five or more, six or more, seven or more,eight or more, nine or more, ten or more or plural powder (or solidcomponent) reservoirs.

Pharmaceutically active agents generally include physiologically orpharmacologically active substances that produce a systemic or localizedeffect or effects in animals, cells, non-humans and humans. When anactive agent is present, any such agent can be used. Exemplary classesof active agents include, by way of example and without limitation,pesticides, herbicides, insecticides, antioxidants, plant growthinstigators, sterilization agents, catalysts, chemical reagents, foodproducts, nutrients, cosmetics, vitamins, sterility inhibitors,fertility instigators, microorganisms, flavoring agents, sweeteners,cleansing agents and other such compounds for pharmaceutical,veterinary, horticultural, household, food, culinary, agricultural,cosmetic, industrial, cleaning, confectionery and flavoringapplications.

Whenever mentioned and unless otherwise specified, the term “activeagent” includes all forms of the active agent including neutral, ionic,salt, basic, acidic, natural, synthetic, diastereomeric, isomeric,enantiomerically pure, racemic, hydrate, chelate, derivative, analog,optically active, optically enriched, free base, free acid,regioisomeric, amorphous, anhydrous and/or crystalline forms.

A three-dimensionally printed dosage form can comprise one, two or moredifferent active agents. Particular combinations of active agents can beprovided. Some combinations of active agents include: 1) a first drugfrom a first therapeutic class and a different second drug from the sametherapeutic class; 2) a first drug from a first therapeutic class and adifferent second drug from a different therapeutic class; 3) a firstdrug having a first type of biological activity and a different seconddrug having about the same biological activity; 4) a first drug having afirst type of biological activity and a different second drug having adifferent second type of biological activity. Exemplary combinations ofactive agents are described herein.

The active agent can be independently selected at each occurrence fromactive agents such as an antibiotic agent, antihistamine agent,decongestant, anti-inflammatory agent, antiparasitic agent, antiviralagent, local anesthetic, antifungal agent, amoebicidal agent,trichomonocidal agent, analgesic agent, anti-arthritic agent,anti-asthmatic agent, anticoagulant agent, anticonvulsant agent,antidepressant agent, antidiabetic agent, antineoplastic agent,anti-psychotic agent, neuroleptic agent, antihypertensive agent,hypnotic agent, sedative agent, anxiolytic energizer agent,antiparkinson agent, muscle relaxant agent, antimalarial agent, hormonalagent, contraceptive agent, sympathomimetic agent, hypoglycemic agent,antilipemic agent, ophthalmic agent, electrolytic agent, diagnosticagent, prokinetic agent, gastric acid secretion inhibitor agent,anti-ulcerant agent, anti-flatulent agent, anti-incontinence agent,cardiovascular agent or a combination thereof. A description of theseand other classes of useful drugs and a listing of species within eachclass can be found in Martindale, The Extra Pharmacopoeia, 31ST Ed. (ThePharmaceutical Press, London 1996), the disclosure of which isincorporated herein by reference in its entirety.

The above-mentioned lists should not be considered exhaustive and aremerely exemplary of the many embodiments considered within the scope ofthe invention. Many other active agents can be included in the powder ofthe invention.

The liquid applied to the powder can be a solution or suspension. Theliquid can comprise an aqueous carrier, nonaqueous carrier, organiccarrier or a combination thereof. The aqueous carrier can be water or anaqueous buffer. The nonaqueous carrier can be an organic solvent, lowmolecular weight polymer, oil, silicone, other suitable material,alcohol, ethanol, methanol, propanol, isopropanol, poly(ethyleneglycol), glycol, other such materials or a combination thereof.

In some embodiments, the equipment assembly comprises one or more, twoor more, three or more, four or more or plural liquid reservoirs. Theliquid can be colored or non-colored. The liquid can comprise pigment,paint, dye, tint, ink or a combination thereof.

The liquid can comprise one or more solutes dissolved therein. Thepowder and/or liquid can comprise one or more binders.

The exemplary embodiments herein should not be considered exhaustive,but merely illustrative of only a few of the many embodimentscontemplated by the present invention.

As used herein, the term “about” is taken to mean a value that is within±10%, ±5% or ±1% of the indicated value.

The entire disclosures of all documents cited herein are herebyincorporated by reference in their entirety.

Example 1

The following materials and procedure are used to preparethree-dimensionally printed dosage forms that dissolve rapidly insaliva.

A powder comprising at least one pharmaceutical carrier is loaded intothe powder reservoir. A fluid comprising a liquid and at least oneactive ingredient is loaded into the fluid reservoir. The equipmentassembly is operated, whereby plural stacked incremental layers ofprinted powder are sequentially formed in build modules by repeatedlypassing the build modules through one or more build stations. Typicallyfour to fifty incremental printed powder layers are formed and adhere toeach other thereby forming a printed bed having one or more articlessurrounded by or embedded in loose powder. The printed beds are dried ina dryer. The printed articles are separated from the loose powder with aharvester. The printed articles are then optionally dedusted with adeduster. The printed articles are then optionally packaged.

The above is a detailed description of particular embodiments of theinvention. It will be appreciated that, although specific embodiments ofthe invention have been described herein for purposes of illustration,various modifications may be made without departing from the spirit andscope of the invention. Accordingly, the invention is not limited exceptas by the appended claims. All of the embodiments disclosed and claimedherein can be made and executed without undue experimentation in lightof the present disclosure.

1.-40. (canceled) 41) A method for the preparation ofthree-dimensionally printed articles with an equipment assembly, themethod comprising: a) initiating operation of a three-dimensionalprinting build system comprising: a conveyor system adapted to conductplural build modules along a circuitous path; plural build modulesengaged with the conveyor system, wherein the build modules are adaptedto receive and temporarily retain powder from a powder layering system;and at least one build station comprising: 1) at least one powderlayering system adapted to form incremental powder layers within buildmodules; and 2) at least one printing system adapted to apply a liquidaccording to a predetermined pattern to incremental powder layers withinbuild modules; b) with the conveyor system, repeatedly transporting thebuild modules from the at least one powder layering system to the atleast one printing system to form a three-dimensionally printed bedcomprising one or more three-dimensionally printed articles in the buildmodules. 42) The method of claim 41 further comprising: a) harvestingthe one or more three-dimensionally printed articles from thethree-dimensionally printed bed with at least one harvesting systemadapted to separate loose powder from the one or morethree-dimensionally printed articles. 43) The method of claim 42 furthercomprising removing liquid from one or more incremental powder layersonto which the liquid has been applied or from the three-dimensionallyprinted bed with at least one liquid removal system, optionally, whereinthe liquid removal system is adapted to process two or more buildmodules at a time. 44) The method of claim 43 further comprisingdedusting the printed articles that have been harvested from a printedpowder bed remove loose particles of powder from printed articles. 45)The method of claim 43 further comprising: a) packaging the one or morethree-dimensionally printed articles with at least one packaging system;b) recovering loose powder generated during the process with a powderrecovery system for recovering, and optionally recycling, unprintedpowder; c) detecting the presence, amount or concentration of liquidpresent in the one or more three-dimensionally printed articles with aliquid detector; or d) inspecting the three-dimensionally printed bedsor the one or more three-dimensionally printed articles with at leaseone inspection system. 46) The method of claim 45, wherein: a) theinspection system is a printed powder inspection system that determinesthe integrity of printing in one or more printed incremental layers orone or more printed articles, or determines whether or not powder wasapplied in one or more incremental layers; b) the inspection system is aprinted article inspection system that determines whether or not one ormore printed articles have the correct size, shape, weight, appearance,density, content or color; c) the inspection system is a liquidapplication inspection system that monitors droplets of liquid appliedby the print head to powder; or d) the inspection system comprises oneor more cameras. 47) The method of claim 46, wherein: a) determining theintegrity of printing comprises at least one of determining whether ornot liquid has been correctly applied to one or more incremental layersaccording to one or more predetermined patterns, or determining whetheror not liquid has been correctly applied to one or more incrementallayers according to a predetermined amount; or b) a camera isindependently selected at each occurrence from the group consisting of avisible wavelength camera, an UV wavelength camera, a near infraredwavelength camera, an x-ray camera and an infrared wavelength camera.48) The method of claim 41 further comprising transferringthree-dimensionally printed beds, one or more at a time, away from thethree-dimensional printing build system with a bed transfer system. 49)The method of claim 48 wherein: a) the bed transfer system transfersthree-dimensionally printed beds to one or more liquid removal systemsor one or more harvesting systems; or b) the transfer system isintegrated or synchronized with the conveyor system, the liquid removalsystem or both. 50) The method of claim 43, wherein: a) the liquidremoval system processes two or more build plates and their contents ata time; b) the liquid removal system processes two or more printed bedsat a time; or c) the liquid removal system processes two or more printedarticles at a time. 51) The method of claim 41 further comprisingcontrolling one or more components the equipment assembly with a controlsystem comprising one or more computerized controllers, one or morecomputers, and one or more user interfaces for one or more computers.52) The method of claim 51, wherein: a) one or more components of thethree-dimensional printing build system are computer controlled; b) theconveyor system, the height adjustable platforms of the build modules,the at least one powder layering system and the at least one printingsystem are computer controlled; or c) the equipment assembly spreadslayers of powder and deposits droplets of liquid in one or morepredetermined patterns onto the layers according to instructionsprovided by a computerized controller. 53) The method of claim 52further comprising providing on one or more two-dimensional image filescomprising pixels, wherein one or more image files define the one ormore predetermined patterns. 54) The method of claim 41, wherein: a) abuild module comprises an incrementally height adjustable platformadapted to receive and temporarily retain at least one incremental layeror plural stacked incremental layers of powder; b) a build modulecomprises a body comprising an upper surface with a cavity, a heightadjustable build platform disposed within the cavity, height adjusterengaged with the body and the platform, and engagement mechanism; c)plural build modules are removably engaged with the conveyor system; d)the build module comprises one or more sidewalls surrounding the buildplate and being adapted to retain powder on the height adjustableplatform; e) the build module further comprises a removable build platedisposed below the upper surface of the build module; or f) the buildmodule is removably engaged with the conveyor system. 55) The method ofclaim 54 further comprising raising or lowering the platform by one ormore increments after placing an incremental layer of powder thereon.56) The method of claim 41, wherein: a) the conveyor system conducts theplural build modules along a planar circuitous path, a horizontalcircuitous path, a vertical circuitous path, or a combination thereof;or b) the conveyor system transports plural build modules along a pathin a counterclockwise direction or clockwise direction. 57) The methodof claim 41, wherein: a) the at least one build station is incrementallyheight adjustable with respect to the build modules, whereby thevertical space between the build module and the build station can beadjusted by one or more increments; or b) the build station isvertically fixed with respect to the build modules and a build platformwithin a build module is vertically height adjustable with respect tothe build module so that the vertical distance between the build stationand the build module remains the same during a print lap or print cycle.58) The method of claim 41, wherein the at least one powder layeringsystem comprises at least one powder fill head that does not move eitherlongitudinally or transversely, with respect to the plane of the uppersurface of a build module, when applying an incremental layer of powderonto the build module or when forming an incremental powder layer on thebuild module. 59) The method of claim 41, wherein the at least oneprinting system comprises at least one print head that does not moveeither longitudinally or transversely, with respect to the plane of theupper surface of a build module, when depositing droplets of liquid ontopowder in the build module or when forming a printed incremental powderlayer in on the build module. 60) The method of claim 41, wherein theconveyor system repeatedly transports the plural build modules from theat least one powder layering system to the at least one printing systemand the printing is performed using Cartesian coordinate based printingand excluding radial or polar coordinate printing. 61) The method ofclaim 41, wherein the method excludes a method wherein liquid is appliedto the powder according to a polar coordinate system. 62) The method ofclaim 41, wherein the invention excludes a method wherein the print headmoves laterally or transversely or is not stationary, with respect to abuild module, while applying liquid to an incremental powder layer. 63)The method of claim 41, wherein the invention excludes a method whereinthe powder fill head moves laterally or transversely or is notstationary, with respect to a build module, while depositing anincremental powder layer. 64.-74. (canceled)